Imidazole-grafted chitosan-mediated gene delivery: in vitro study on transfection, intracellular trafficking and degradation

Nanomedicine (Lond). 2011 Nov;6(9):1499-512. doi: 10.2217/nnm.11.51. Epub 2011 Oct 20.

Abstract

Aim: To study the mechanism of transfection mediated by imidazole-grafted chitosan (CHimi) nanoparticles, to propose new strategies to control and improve the expression of a delivered gene in the context of regenerative medicine.

Methods: Biochemical and microscopy methods were used to establish transfection efficiency and nanoparticle intracellular trafficking. The role of CHimi and degree of N-acetylation (DA) on transfection was explored.

Results: CHimi was found to promote the expression of a delivered gene during a minimum 7-day period. Additionally, the production of a protein of interest could be upheld by consecutive transfections, without compromising cell viability. Transfection was found to be a time-dependent process, requiring CHimi-DNA complex disassembling. The DA was found to have an impact on transfection kinetics in line with the observation that the rate of lysozyme-mediated nanoparticle degradation increases with the polymer DA.

Conclusion: The adjustment of the CH degradation rate can be used as a tool for tuning the expression of a gene delivered by CH-based nanoparticle systems.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line
  • Chitosan / chemistry*
  • Gene Transfer Techniques
  • Humans
  • Imidazoles / chemistry*
  • Nanoparticles / chemistry
  • Nanotechnology / methods
  • Transfection / methods*

Substances

  • Imidazoles
  • imidazole
  • Chitosan